Oral + Rapid Oral Abstract session

This daily highlight in skin cancer is presented by Dr Iris Dirven (Vrije Universiteit Brussel), who has selected some interesting presentations from oral abstract sessions on melanoma and non-melanoma skin cancer at ASCO 2025.

Two phase 3 trials in the adjuvant treatment of melanoma were reported. The first, the Relativity-098 trial, compared nivolumab monotherapy to the combination of nivolumab and relatlimab in patients with completely resected stage III and IV melanoma. This study did not show a statistically significant benefit for the combination therapy, confirming that nivolumab remains the standard of care in this setting.

The second phase 3 study, the Columbus AD trial, investigated the use of adjuvant encorafenib and binimetinib versus placebo in patients with resected stage IIB and IIC BRAF-mutant melanoma. The trial was prematurely closed due to slow patient recruitment and therefore did not achieve its efficacy objectives. Although the data suggest that adjuvant BRAF-MEK inhibition in this early-stage setting is safe, there is currently no robust evidence to support its efficacy.

In the neoadjuvant setting, a Phase 2 trial investigated the use of pembrolizumab before and after surgery in patients with stage IIB/C melanoma. The aim was to reduce the incidence of sentinel lymph node positivity compared to historical controls. While the overall population did not meet the pre-specified goal of reducing sentinel node positivity by 50%, a promising signal was observed in the stage IIC subgroup, which typically carries a higher risk of recurrence. However, the study used a uniform treatment approach for all stage IIB/C patients. Future strategies are likely to require biomarker-driven selection to identify those who would benefit most from early systemic therapy. Ongoing trials, such as the NeoSenti study in Belgium, aim to refine patient selection using gene expression profiles or clinical nomograms.

A second notable phase 2 study, SWOG S2000, addressed treatment for patients with symptomatic melanoma brain metastases, a particularly challenging subgroup. Patients received either the standard combination of nivolumab and ipilimumab or a triplet of encorafenib, binimetinib, and an anti-PD-1. Results showed a higher six-month PFS rate in the triplet arm, although the study was underpowered for definitive conclusions. The data point to the potential utility of combining targeted therapy with immunotherapy in select patients and warrant further investigation in larger trials.

Beyond systemic therapy, promising developments in cell-based treatments for melanoma were presented. An update on lifileucel, a tumour-infiltrating lymphocyte (TIL) therapy, showed that approximately 20% of heavily pretreated metastatic melanoma patients remained alive at five years, despite a modest initial response rate. This suggests that for those who respond, TIL therapy may offer durable benefit.

A novel TIL platform, OBX-115, incorporates membrane-bound IL15 and can be regulated with acetazolamide, thereby reducing the need for high-dose lymphodepleting chemotherapy. Patients also do not require a high-dose IL-2 regimen after TIL infusion. This innovation lowers toxicity and could expand the eligibility of patients for TIL treatment. A phase 3 trial is underway, and this approach could become part of future melanoma treatment algorithms, particularly for patients who cannot tolerate more toxic regimens.